The project consists of a series of clinical trials evaluating the clinical efficacy and safety of experimental therapeutic agents for the control of acute pain in ambulatory patients undergoing minor surgical procedures. The surgical removal of impacted third molars serves as a model of minor surgery with associated intraoperative and postoperative pain. All studies are double-blind with randomly allocated, parallel treatment groups and multiple dependent measures of therapeutic efficacy and clinical safety. Recent studies provide evidence for a locally-mediated mechanism of action: administration into the extraction sites results not only in significantly less pain than following oral administration of the same formulation but with substantially lower blood levels of the drug. The results of these studies support the hypothesis being evaluated that peripheral administration of an NSAID at low doses results in greater analgesic efficacy and a lower incidence of side effects by minimizing systemic exposure. Two parallel studies evaluated the analgesic efficacy of a neurokinin-1 receptor antagonist. Results of the studies demonstrated a transient effect in comparison to placebo, with the positive control (ibuprofen) providing a prolonged suppression of pain in the immediate postoperative time point. Three other studies have demonstrated that oral surgery is a useful model of control hyperalgesia with both local anesthetics with an antagonist of the NMDA receptor reducing pain at 48 hours.